The clonal structure and dynamics of the human T cell response to an organic chemical hapten

Elife. 2021 Jan 12:10:e54747. doi: 10.7554/eLife.54747.

Abstract

Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis and is used in the treatment of warts, melanoma, and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a dynamic Bayesian network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens.

Keywords: Bayesian network; T cell receptor; cdr3 motif; contact dermatitis; human; immunology; inflammation; patch test; repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allergens / pharmacology*
  • Child
  • Cyclopropanes / pharmacology*
  • Female
  • Haptens / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology*
  • Young Adult

Substances

  • Allergens
  • Cyclopropanes
  • Haptens
  • Receptors, Antigen, T-Cell
  • diphenylcyclopropenone

Associated data

  • SRA/PRJNA592875

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.